A variety of lubricious coatings have been proposed for use on the surfaces of medical devices such as, for example, catheters, guide wires, endotracheal tubes and implants. Common materials used in the art to provide lubricious coatings for medical devices include, for example, oil, silicone, and polymeric materials, such as poly(N-vinylpyrrolidone), hydrophilic polyurethanes, Teflon, poly(ethylene oxide) and poly(acrylic acid). Among the most common materials used to provide lubricious coatings are hydrophilic polymers which are covalently bonded to the substrate with a binder polymer having reactive functional groups, e.g., isocyanate, aldehyde, and epoxy groups. Other binder polymers comprise, for example, copolymers containing a vinyl moiety. Details of such coatings are disclosed, for example, in U.S. Pat. Nos. 5,091,205 issued Feb. 25, 1992 and 5,731,087 issued Mar. 24, 1998.
Medical device coatings that are visible in magnetic resonance imaging (MRI) provide the opportunity to use magnetic resonance to perform therapeutic procedures. The possible uses of image guided therapy otherwise known as interventional MR are extensive. Examples of these applications include monitoring ultrasound and laser ablations, guiding the placement of biopsy needles, endovascular therapy, and visualizing disease, such as tumors, inter-operatively. This type of interventional therapy eliminates the hazards of ionizing radiation associated with x-ray fluoroscopy. At the same time, it acquires real-time images in three dimensions and due to the sensitivity of the MR to the test tissue environmental it can also provide additional diagnostic information. As used herein, the term “real-time” means that the visualization of the medical device is synchronized with the movement of the device in the body of the patient.
MRI shares the same underlying theory as nuclear magnetic resonance (NMR). Contrast is obtained when water protons in of the test tissue have shorter relaxation times relative to the protons of other water molecules in the environment around the tissue. Contrast can be enhanced by the presence of an agent that can shorten the relaxation time of water protons even further. Such agents operate in the following manner. When protons are pulsed with a radio-frequency pulse in a magnetic field, their nuclear dipoles are a certain angle out of phase with the applied magnetic field. Longitudinal relaxation is the drift back of the protons back to their original alignment with the magnetic field. Paramagnetic contrast agents facilitate this relaxation process by accommodating the excess energy from the protons caused by the pulsing. Gadolinium has become the paramagnetic ion most often used in the art because it has the largest number of unpaired electrons in the 4f orbitals and therefore exhibits the greatest longitudinal (T1) relaxivity of any element. In the presence of gadolinium, some of the magnetic energy of the nuclei in the high-energy state can transfer energy to gadolinium and the gadolinium can accept this energy because of its magnetic susceptibility.
Alternatively, contrast in magnetic resonance is also commonly achieved using super-paramagnetic particles. Typically, iron oxide nanoparticles are used because can they enhance the rate of the spin-spin or T2 (transverse) relaxation. This is accomplished in the following way. After a 90° radio-frequency pulse in the x direction, a magnetization component appears in the y direction. This can be pictured as the nuclear dipoles bunched together and precessing around the surface of a double cone transverse to the applied magnetic field. This condition is called phase coherence. Super-paramagnetic particles cause inhomogeneities in the applied magnetic field resulting in different effective magnetic fields for each of the nuclei. These inhomogeneities cause the nuclei to lose phase coherence at a faster rate relative to proton nuclei that are not in the presence of super-paramagnetic particles.
In order to detect medical devices in using MRI, gadolinium complexes have been grafted onto the surface of polymer substrates. For example, in PCT patent application publication number WO 99/60920, there is disclosed a magnetic resonance (MR) signal-emitting coating which includes a paramagnetic metal ion-containing polymer complex and a method of visualizing medical devices in magnetic resonance imaging, which includes the step of coating the devices with the paramagnetic-ion containing polymer. The patent application further discloses a coating for visualizing medical devices in magnetic resonance imaging, comprising a complex of formula (I):P-X-L-Mn+  (I)Wherein P is a polymer, X is a surface functional group, L is a chelate, M is a paramagnetic ion and n is an integer that is 2 or greater. Benefits may be realized from the approach disclosed in the patent application over the “active visualization” technique method since it eliminates the need for the incorporation of RF coils and transmitting wires into the device and it provides visualization of the complete device and not merely the tip. However, this approach appears to be complex because of the necessity to engage in chemical grafting and plasma treatment. Further, it is believed to be extremely difficult to implement for a commercial-scale application.
Consequently, a simple coating process that is compatible with current hydrophilic, lubricious coating technology to impart such MRI capability to a medical device is desired in the art.